Interleukin-4 Drives Tumor-Associated Macrophage Polarization to Promote Tumor Gr

描述(申请人提供)：尽管在抗癌斗争中取得了许多进展，但在美国，癌症仍然是一个令人恐惧的诊断和主要死亡原因。这项拟议研究的理由和希望是，通过低估癌症如何进展和渗透到人体各部位而获得的任何和所有知识，不仅使科学家，而且使患者和公众更接近于实现彻底根除癌症的共同目标。众所周知，肿瘤周围的环境是一种阴燃的炎症，一种被称为肿瘤相关巨噬细胞()的细胞类型在这种环境中普遍存在，已被证明促进癌症的许多方面。TAMs以多种方式促进肿瘤进展；它们支持新的肿瘤血管生长、肿瘤细胞侵袭，甚至促进转移。这项提议的一个关键目标是了解刺激细胞信号的来源 的促肿瘤作用以及这些信号如何作用于TAMS。这项拟议的研究与公共健康相关，因为了解所有影响癌症生长和转移的来源和因素--无论是来自肿瘤还是来自身体--最终将导致如何预防肿瘤的发现。因此，这项研究与美国国立卫生研究院寻求基础知识以减轻疾病负担和延长生命的任务直接相关。为实现这一目标所采用的方法将是研究小鼠的肿瘤模型。肿瘤会产生分泌或不分泌某种信号--白介素4(IL-4)，然后 这些肿瘤是在有或没有产生IL-4能力的小鼠身上进行研究的。此外，还将研究IL-4及其对有和没有IL-4受体的TAM的影响，以帮助识别它可能如何在促进癌症方面发挥作用。这个项目的具体目标是确定肿瘤分泌的IL-4对肿瘤生长、转移和TAM的影响，并了解IL-4是如何向TAM发出信号以实现其亲癌后果的。预计这项研究结果的影响将是允许研究人员从多个途径针对TAMs进行未来的抗癌治疗。

DESCRIPTION (provided by applicant): Despite many advances in the battle against cancer, it remains a dreaded diagnosis and a leading cause of death in the United States. The rationale and hope for this proposed research is that any and all knowledge gained in understating how cancer progresses and infiltrates areas of the body brings, not only scientists, but the patients and public closer to achieving their common goal of complete eradication of cancers. The environment surrounding tumors is known to be one of smoldering inflammation and one cell type, known as a tumor-associated macrophage (TAM), prevalent in this environment has been shown to promote many aspects of cancer. TAMs foster tumor progression in multiple ways; they support new tumor blood vessel growth, tumor cell invasion, and even enhance metastasis. A key objective of this proposal is to understand the origin of the cellular signals that stimulate TAM's pro-tumor functions and how these signals act on TAMs. The proposed research is relevant to public health because understanding all of the sources and factors that influence cancer growth and metastasis - be they from the tumor or the body - will ultimately lead to discoveries of how to prevent tumors. Thus, this research is directly relevant to the NIH mission to seek fundamental knowledge that will reduce the burden of illness and lengthen life. The methods employed in order to achieve this goal will be to study tumor models in mice. Tumors will be generated that either do or do not secrete a certain signal, interleukin-4 (IL-4), and then these tumors investigated in mice that either do or do not have the ability to produce IL-4. Also, IL-4 and its effects on TAMs both with and without the IL-4 receptor will be studied to help discern how it might play a role in promoting cancer. The specific aims of this project are to determine the effects of IL-4 secreted from the tumor on tumor growth, metastasis, and TAMs and to understand how IL-4 signals to TAMs to achieve its pro- cancer consequences. It is expected that the impact of the results of this study will be in allowing researchers to target TAMs with future anti-cancer therapy from multiple avenues.